Inclusion Criteria:

          -  Patients must have histologically confirmed progressive brain metastases from melanoma
             or recurrent/progressive malignant glioma (glioblastoma, anaplastic glioma), for which
             standard curative or palliative measures, with the exception of surgery, do not exist
             or are no longer effective

          -  Patients must have measurable disease in the brain, defined as at least one lesion
             that can be accurately measured in at least one dimension as >= 10 mm by brain
             magnetic resonance imaging (MRI); MRI of the brain (with and without gadolinium
             enhancement) is to be performed using standard 5-mm slices with 2.5-mm spacing for
             comparison to subsequent MRI scans

          -  In the case of malignant glioma patients, they must have previously undergone
             standard-of-care treatment including surgery, radiation, and first line adjuvant
             chemotherapy prior to the experimental treatment (WP1066); in the case of melanoma
             patients with brain metastasis, they may have previously undergone a resection (with
             radiographic evidence of progression), have undergone gamma knife radiosurgery (with
             radiographic evidence of progression), or have been treated with other systemic
             therapies that failed

          -  Karnofsky performance scale score >= 60%

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,000/mcL

          -  Platelets >= 75,000/mcL

          -  Total bilirubin =< 1.6

          -  Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal

          -  Creatinine within normal institutional limits OR creatinine clearance >= 60
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Prothrombin time (PT)/partial thromboplastin time (PTT) < 1.5 x normal institutional
             standard

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Melanoma patients must be intolerant of, or have disease that has proven refractory to
             approved therapies such as BRAF or MEK inhibitors for BRAF-positive metastatic
             melanoma and/or checkpoint blockade with either anti-PD1 or anti-CTLA-4 for metastatic
             melanoma

          -  Willing and able to tolerate brain MRI's with contrast

          -  Patients with stable seizures (e.g., no seizures for >= 14 days and not requiring
             escalation or addition of anti-epileptic drugs for 14 days from starting treatment)
             will be eligible

          -  Patients who are eligible for the surgical expansion cohort are identified by the
             clinical team who have made the independent decision that the patient would benefit
             from non-emergent palliative surgical resection (i.e. they are not a candidate for
             gamma knife or other type of standard therapy)

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas) prior to entering the study or those who have not recovered from adverse
             events due to agents administered more than 4 weeks earlier; biological agents, immune
             modulators, and targeted therapeutic approaches require a 2-week washout window

          -  Patients who are receiving any other investigational agents require a 4 week washout
             period; patients who have received cellular or gene therapy at any time are not
             eligible

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to WP1066

          -  The enzymatic metabolism profile of WP1066 is unknown; patients who are receiving
             drugs that significantly interact with the cytochrome P450 (CYP450) enzyme(s) are
             ineligible; however, if they are switched to other medications with a 2-week washout
             window, they will be eligible; patients are also excluded if they have been exposed
             within 7 days of planned first study treatment day to medications that are
             predominantly cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6),
             cytochrome P450, family 2, subfamily C, polypeptide 9 (2C9) or cytochrome P450, family
             2, subfamily C, polypeptide 19 (2C19) substrates, strong inhibitors or inducers, and
             sensitive substrates of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
             with narrow therapeutic range; patients requiring escalation of the corticosteroid
             dose will be excluded, but patients receiving a stable or decreasing dose for at least
             one week will be eligible

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  No single lesion can be larger than 3 cm in maximal diameter; there may not be midline
             shift exceeding 5 mm or hydrocephalus

          -  Pregnant women are excluded from this study because WP1066 could potentially be
             teratogenic or have abortifacient effects; breastfeeding should be discontinued if the
             mother is treated with WP0166; female subjects of childbearing potential should be
             willing to use 2 methods of birth control prior to study entry, during the study, and
             for 2 months after the last dose of the study drug or be surgically sterile; subjects
             of childbearing potential are those who have not been surgically sterilized or have
             not been free from menses for > 1 year; should a woman become pregnant or suspect she
             is pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately; men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and 4 months after completion of WP1066 administration

          -  Human immunodeficiency virus (HIV)-positive patients receiving combination
             antiretroviral therapy are ineligible because of the potential for pharmacokinetic
             interactions with WP1066

          -  Patients who have received bevacizumab, Gliadel, or are on active therapy with Optune
             are not eligible

          -  The potential for further hemorrhaging with the use of WP1066 is unknown; furthermore,
             because brain melanoma metastases commonly hemorrhage, toxicity may be inappropriately
             attributed to WP1066 in this setting; it will be at the principal investigator's (PIs)
             discretion to enroll a patient who has a small, asymptomatic brain hemorrhage, but
             patients who have had symptomatic hemorrhages will be excluded

          -  Patients with uncontrolled seizures or seizure requiring escalation or addition of
             anti-epileptic drugs will be excluded

          -  Because one of the secondary objectives is PFS based on radiographic volumetric
             analysis of the tumor, the presence of diffuse leptomeningeal disease will be an
             exclusion criterion for this study; this is secondary to the inadequacy of measuring
             the extent of the tumor burden within this setting and the very poor prognosis of
             these patients

          -  The cardiac toxicities of WP1066 are unknown; thus, patients who have a corrected QT
             (QTc) interval > 450 ms at base line will be excluded; concomitant use of agents that
             prolong the QT interval will be avoided

          -  Malignant glioma patients within 12 weeks of completion of radiation concurrent
             temozolomide will be excluded

          -  Melanoma patients with large or symptomatic brain metastasis, and in whom
             neurosurgical removal is indicated will not be eligible for this trial