Inclusion Criteria:

          -  Age ≥ 18 years with a recurrent, primary CNS neoplasm. Primary CNS neoplasms included
             in this study: glioblastoma and glioblastoma histologic subtypes, gliosarcoma, primary
             CNS sarcomas, anaplastic glial neoplasms including anaplastic astrocytoma, anaplastic
             oligodendroglioma, anaplastic mixed neuronal-glial tumors, and pilocytic astrocytoma
             with anaplastic features, diffuse astrocytoma, oligodendroglioma, gliomatosis cerebri,
             pleomorphic xanthoastrocytoma, anaplastic pleomorphic xanthoastrocytoma, diffuse
             midline gliomas and histone mutated gliomas, ependymoma, anaplastic ependymoma, and
             all ependymoma subtypes, medulloblastoma and all medulloblastoma subtypes, ATRT,
             primary CNS embryonal/primitive neuroectodermal tumors, atypical and anaplastic
             meningiomas, choroid plexus tumors, and pineal region tumors.

          -  Advanced disease after having received established standard of care treatment for
             their disease and have no standard treatment options available

          -  Karnofsky Performance Score (KPS) of greater than or equal to 70.

          -  Measurable or evaluable disease defined by RANO criteria. The exception will be
             patients who have had surgery in the past 4 weeks, patients who are post-operative
             after a maximal resection will be allowed to enroll after 4 weeks from surgical
             resection.

          -  Washout for prior investigational or approved cytotoxic chemotherapy is 28 days prior
             to the first dose of ONC206; 42 days in the case of nitrosoureas; 28 days or 5
             half-lives (whichever is less; but not less than 14 days) in case of investigational
             or approved molecularly targeted agent; 14 days in the case of radiotherapy.

          -  Patients will be required to enroll on the NCI Neuro-Oncology Branch natural history
             study (16-C-0151).

          -  No major surgery in the prior 4 weeks

          -  Patients must have normal organ and marrow function as defined below:

          -  An available tumor specimen (paraffin-embedded block and/or frozen tissue) from prior
             resection or biopsy, ≥15 unstained slides for IHC analysis.

          -  Ability to swallow oral capsules.

          -  Ability to tolerate an MRI study with intravenous gadolinium contrast.

          -  Men and women must use double barrier contraceptives

        Exclusion Criteria:

          -  Prior bevacizumab for treatment of high-grade glioma

          -  Known HIV-positive test on combination antiretroviral therapy

          -  Active cardiac disease

          -  Ischemic or hemorrhagic stroke in last 3 months

          -  Refractory epilepsy and patients with primary or secondarily generalized seizures in
             the 28 days before enrollment are excluded. Peri-operative seizures occurring within 7
             days of surgery with resolution by day 8 after surgery are allowable. Patients must be
             on stable doses of one or two seizure medications for 14 days prior to study
             enrollment.

          -  Impairment of gastrointestinal (GI) function

          -  Concurrent use of warfarin sodium or other Coumadin-derivative anti-coagulants

          -  Concurrent use of strong inhibitors or inducers of CYP3A4, 2D6, 1A2, 2C9 and 2C19 are
             excluded at least 14 days prior to and throughout the study.