Inclusion Criteria:

          1. 2 to less than 19 years of age.

          2. Patient body weight must be above the minimum necessary for the patient to receive the
             ONC201 dose indicated for the currently enrolling dose level. The minimum body weight
             ranges from 10-27.5kg depending on the dose level.

          3. Arm A and G: Patients with glioma who are positive for the H3 K27M mutation (positive
             testing in CLIA laboratory) and have completed at least one line of prior therapy.
             Evidence of progression is not required so that ONC201 may be administered to patients
             in the maintenance setting or to patients with recurrent disease. No more than two
             episodes of recurrence from radiotherapy and/or chemotherapy are allowed. Use of
             bevacizumab solely for treatment of radiation necrosis, pseudoprogression, or
             treatment effect will not be considered a recurrence. Post-mortem biopsy is required
             if H3 K27M status of tumor is unknown and archival tumor tissue not available.

             Arm B: Patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG), defined
             as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible
             with or without histologic confirmation. Post-mortem biopsy is required if H3 K27M
             status of tumor is unknown and archival tumor tissue not available.

             Arm C: Patients with midline gliomas are eligible with or without histologic
             confirmation and must be eligible for tumor biopsy as deemed by the site Investigator.

             Arm D: Patients with recurrent glioma who are positive for the H3 K27M mutation
             (positive testing in CLIA laboratory), have completed at least one line of prior
             therapy, must be willing to undergo serial lumbar puncture to obtain cerebrospinal
             fluid (CSF), and must be scheduled to undergo sedated MRIs. Local anesthesia for
             spinal tap is also allowed. Evidence of progression is not required so that ONC201 may
             be administered to patients in the maintenance setting or to patients with recurrent
             disease. No more than two prior episodes of recurrence from radiotherapy and/or
             chemotherapy are allowed. Use of bevacizumab solely for treatment of radiation
             necrosis, pseudoprogression, or treatment effect will not be considered a recurrence.
             Spinal tap should not be performed if treating clinician or lumbar puncture
             proceduralist has concern of signs of elevated intracranial pressure, including recent
             worsening in headache or somnolence.

             Arm E: Patients with glioma who are positive for the H3 K27M mutation (positive
             testing in CLIA laboratory) or have diagnosed diffuse intrinsic pontine glioma (DIPG),
             defined as tumors with a pontine epicenter and diffuse involvement of the pons, are
             eligible with or without histologic confirmation. Patients must be 2-12 weeks from
             completion of first-line radiation. Evidence of progression is not required so that
             ONC201 may be administered to patients in the maintenance setting or to patients with
             recurrent disease.

             Arm F:

             Pediatric patients with histologically confirmed diagnosis of high-grade glioma in any
             tumor sample with a known histone H3 K27M mutation identified by IHC or DNA sequencing
             test performed in a CLIA setting. Evidence of progressive disease on contrast-enhanced
             brain MRI as defined by RANO-HGG criteria is required. Patients must have had previous
             therapy with at least radiotherapy.

          4. Karnofsky ≥ 50 for patients ≥ 16 years of age, and Lansky ≥ 50 for patients < 16 years
             of age. For Arm F, Karnofsky ≥ 60 for patients ≥ 16 years of age, and Lansky ≥ 60 for
             patients < 16 years of age

          5. From the projected start of scheduled study treatment, the following time periods must
             have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic
             therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from
             antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor
             therapies. For patients who have received radiotherapy, patients in any arm must be at
             least 2 weeks from the completion of local palliative radiotherapy (re-irradiation for
             progressive disease or upfront radiation at initial diagnosis). For Arm F, patients
             must be at least 90 days from prior radiation to the first dose of ONC201unless the
             progressive lesion is outside of the high-dose radiation target volume or there is
             unequivocal evidence of progressive tumor on a biopsy specimen.

          6. Adequate organ function defined as:

             Bone Marrow:

               -  Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 and

               -  Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving
                  platelet transfusions for at least 7 days prior to enrollment).

             Renal Function:

             • Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥
             70mL/min/1.73 m2 or normal serum creatinine based on age as shown below or GFR >
             70ml/min/1.73m^2: Age < 5 years: 0.8 mg/dL maximum Age 5 to < 10 years: 1.0 mg/dL
             maximum Age 10 to < 15 years: 1.2 mg/dL maximum Age > 15 years: 1.5 mg/dL maximum

             Liver Function:

               -  Total Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of
                  institutional normal and

               -  SGPT (ALT) ≤ 110 U/L and

               -  Serum albumin ≥ 2 g/dL.

             Neurologic Function:

             • Patients with seizure disorder may be enrolled if seizure disorder is well
             controlled.

          7. Ability to understand a written informed consent document, and the willingness to sign
             it. Assent will be obtained when appropriate based on the subjects age.

          8. All adverse events Grade > 1 related to prior therapies (chemotherapy, radiotherapy,
             and/or surgery) must be resolved to grade 1 or baseline, except for alopecia and
             sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based
             on investigator's judgment, are acceptable.

          9. For patients post pubertal: Female patients must agree to use effective contraception
             during the period of the trial and for at least 90 days after completion of treatment.
             Male patients must be surgically sterile or must agree to use effective contraception
             during the period of the trial and for at least 90 days after completion of treatment.
             The decision of effective contraception will be based on the judgment of the principal
             investigator.

         10. Corticosteroid dose must be stable or decreasing for at least 3 days prior to the
             baseline CT or MRI scan.

         11. MRI brain and entire spine MRI within 14 days prior to start of study drug for Arms A,
             B, C, E, F and G. Subjects undergoing screening for Arm D must have an MRI of brain
             and entire spine within 3 months prior to start of study drug. Subjects in Arm D will
             have a baseline MRI of brain and spine with lumbar puncture after study consent is
             signed and other eligibility criteria are fulfilled.

         12. For Arms A, B, C, D, F and G: Ability to swallow and retain orally administered
             capsules.

         13. Archival tumor specimen: Subjects in all arms must submit at least 5 unstained slides
             from a tumor specimen that harbors H3 K27M mutation if archival tissue is available.
             For subjects in Arms A, B, E or G, if no archival tumor tissue is available, or if H3
             K27M status of tumor is unknown, then subjects must agree to submit a post-mortem
             biopsy specimen. Subjects in Arm C do not require prior tumor biopsy or confirmation
             of the presence of the H3 K27M mutation. Subjects in Arm D must have confirmation of
             the presence of the H3 K27M mutation in any glioma sample prior to enrollment.
             Subjects in Arm F must submit at least 5 unstained slides from a tumor specimen that
             harbors H3 K27M mutation. Note that the H3 K27M mutation is often reported as H3 K28M
             in gene sequencing assays.

        Exclusion Criteria:

          1. For Arms A, B, D, E, F and G: Evidence of diffuse leptomeningeal disease or evidence
             of CSF dissemination.

          2. Current or planned participation in a study of another investigational agent or using
             an investigational device.

          3. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ONC201 or its excipients.

          4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection or psychiatric illness/social situations that would limit compliance with
             study requirements.

          5. Any known clinically significant active infection including bacterial, fungal or viral
             including hepatitis B (HBV), hepatitis C (HCV) or any underlying disease or in the
             recent past which could compromise enrollment and safety of the patient

          6. Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias
             or bradycardia, unless arrhythmia is controlled and after Cardiology has cleared
             patient to receive ONC201. Receiving therapeutic agents known to prolong QT interval
             will be excluded, however the use of Zofran is permitted. History of CHF, or MI or
             stroke in the last 3 months will be excluded.

          7. Active illicit drug use or diagnosis of alcoholism.

          8. Known additional malignancy that is progressing or requires active treatment within 3
             years of start of study drug.

          9. Concomitant use of potent CYP3A4/5 inhibitors during the treatment phase of the study
             and within 72 hours prior to starting study drug administration.

         10. Concomitant use of potent CYP3A4/5 inducers, which include enzyme inducing
             antiepileptic drugs (EIAEDs) (see Appendix B), during the treatment phase of the study
             and within 2 weeks prior to starting treatment. Concurrent dexamethasone is allowed.

         11. For Arm F: Exclusively non-contrast-enhancing disease or primary malignant lesion
             located in the pons or spinal cord.

         12. For Arm F: Atypical non-astrocytic histologies such as ependymoma, ganglioma and
             pleomorphic xanthoastrocytoma, pilocytic astrocytoma, or pilocytic astrocytoma and
             subependymal giant cell astrocytoma (SEGA).

         13. Prior treatment with ONC201