Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlledXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on anticonvulsants and well controlledXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on anticonvulsants and well controlledXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlledXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on non-enzyme inducing anti-convulsants and well controlledXx_NEWLINE_xXSTEP I: Patients must not have active, uncontrolled seizure disorder; patients must have had no seizures in the last 6 monthsXx_NEWLINE_xXPatients with a history of uncontrolled seizure disorder; including focal or generalized seizure may not have had a seizure within one year prior to registrationXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on anticonvulsants and well controlled; however, drugs that induce CYP3A4/5 (carbamazepine, oxcarbazepine, phenytoin, primidone, phenobarbital) should be avoidedXx_NEWLINE_xXPatients with uncontrolled seizure disorder are not eligible; (patients with seizure disorders that do not require antiepileptic drugs, or are well controlled with stable doses of antiepileptic drugs remain eligible)Xx_NEWLINE_xXCentral nervous system function defined as:\r\n* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled\r\n* Patients must not be in status epilepticus, a coma or on assisted ventilation at the time of study enrollmentXx_NEWLINE_xXConcomitant medications known to lower the seizure threshold discontinued or substituted at least 4 weeks (30 days) prior to Step 1 registrationXx_NEWLINE_xXHistory of any of the following:\r\n* Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to Step 1 registration)\r\n* History of documented inflammatory bowel disease\r\n* Transmural myocardial infarction within the last 4 months prior to Step 1 registration\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to Step 1 registration\r\n* History of any condition that in the opinion of the investigator, would preclude participation in this studyXx_NEWLINE_xXPatients with a known seizure disorder who are receiving non-enzyme inducing anticonvulsants and have well-controlled seizures may be enrolledXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on anti-convulsants and well controlledXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on anticonvulsants and well controlledXx_NEWLINE_xXPatients with active seizures or a history of uncontrolled seizure disorder, including focal or generalized seizure within the past yearXx_NEWLINE_xXSeizure disorders requiring anticonvulsant therapy.Xx_NEWLINE_xXHistory of seizure disorder or active use of anticonvulsantsXx_NEWLINE_xXDocumented history of or current brain metastases due to seizure riskXx_NEWLINE_xXPatients with a history of seizure disorder requiring antiepileptic medication or brain metastases with seizures are NOT eligible for participationXx_NEWLINE_xXHistory of seizures, prior traumatic brain injury, prior stroke, or other predisposing risk of seizure (excluding CNS metastasis)Xx_NEWLINE_xXHistory of uncontrolled seizure disorderXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure including, but not limited to, underlying brain injury, stroke in the past 6 months, primary brain tumors, brain metastasesXx_NEWLINE_xXCurrent or history of seizure disorderXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXSubject has a history of seizure or any condition that may predispose to seizure including, but not limited to, underlying brain injury, stroke in the past 6 months, primary brain tumors, brain metastases, prior seizuresXx_NEWLINE_xXPatients who have an uncontrolled seizure disorder, or active neurological diseaseXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, prior head or traumatic brain injury with loss of consciousness, prior or current space-occupying lesion in the brain); also, history of loss of consciousness or transient ischemic attack within 12 months of day 1 visitXx_NEWLINE_xXSubjects with a seizure disorder that is not well controlled or who have required a change in seizure medications within 60 days of enrollment to the trial.Xx_NEWLINE_xXHistory of seizure disorder.Xx_NEWLINE_xXhistory of seizure disorderXx_NEWLINE_xXSeizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke or transient ischemic attack within 1 year prior to first dose, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect); loss of consciousness within 12 months may be permitted upon discussion with study principle investigator (PI)Xx_NEWLINE_xXMedications known to lower the seizure threshold must be discontinued or substituted prior to study treatment initiationXx_NEWLINE_xXHistory of idiopathic seizure disorder schizophrenia, or psychosis unrelated to glioblastoma, corticosteroid, or anti-epileptic medications.Xx_NEWLINE_xXPatients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlledXx_NEWLINE_xXMedications known to lower the seizure threshold (see Appendix 1) must be discontinued or substituted at least 4 weeks prior to study entry.Xx_NEWLINE_xXSeizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)Xx_NEWLINE_xXPatients with a seizure disorder should be well controlledXx_NEWLINE_xXPatients with seizure disorder may be enrolled if seizure disorder is well controlledXx_NEWLINE_xXConcomitant medications with another A1R antagonist that would increase the risk of seizure (e.g., theophylline, aminophylline).Xx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXHistory of seizure or condition that may predispose to seizure; also, history of loss of consciousness or transient ischemic attack within 12 months of (day 1 visit)Xx_NEWLINE_xXPatients with seizure disorder may be enrolled if receiving non-enzyme inducing anticonvulsants and well controlledXx_NEWLINE_xXHistory of documented seizure disorder, presence of cerebellar dysfunction, dysphasia or altered mental status on neurological examinationXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled.Xx_NEWLINE_xXPatients with history of seizure as an adult including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Also current or prior treatment with anti-epileptic medications for the treatment of seizures. Transient ischemic attack within 12 months prior to study enrollment will not be permitted.Xx_NEWLINE_xXContraindication to the use of bupropion including seizure disorder or conditions that increase the risk of seizure (including bulimia and/or anorexia nervosa, central nervous system [CNS] tumor, severe stroke, abrupt withdrawal from benzodiazepines or alcohol)Xx_NEWLINE_xXPatients who have a history of a seizure disorder requiring anti-seizure medication.Xx_NEWLINE_xXHistory of seizure disorder not related to underlying cancerXx_NEWLINE_xXHistory of seizure disorder requiring antiepileptic medication or brain metastases with seizuresXx_NEWLINE_xXSerum albumin ? 2 g/dL. Neurologic Function: • Patients with seizure disorder may be enrolled if seizure disorder is well controlled.Xx_NEWLINE_xXHistory of seizure, seizure disorder, or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (day 1 visit). Drugs may not be used which are known to decrease the seizure thresholdXx_NEWLINE_xXResearch participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathyXx_NEWLINE_xXResearch participant does not have uncontrolled seizure activity following surgery prior to starting the first T cell doseXx_NEWLINE_xXHistory of seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvementXx_NEWLINE_xXHistory of seizure or any condition that may increase the patient’s seizure risk. Also, history of loss of consciousness or transient ischemic attack within 12 months of day 1Xx_NEWLINE_xXPatients with known seizure disorder must have seizures adequately controlled with non- enzyme inducing antiepileptic medicationsXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, prior head or traumatic brain injury with loss of consciousness, prior or current space-occupying lesion in the brain); also, history of loss of consciousness or transient ischemic attack within 6 months of enrollmentXx_NEWLINE_xXUse of medications known to lower the seizure threshold within 4 weeks prior to study entryXx_NEWLINE_xXHistory of seizure disorderXx_NEWLINE_xXDiagnosis of seizure disorderXx_NEWLINE_xXSeizures disorder not controlled by anti-seizure medicationsXx_NEWLINE_xXSubjects with CNS involvement may be included on the study as long as they have not had any seizure activity in past 4 weeksXx_NEWLINE_xXAny chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a childXx_NEWLINE_xXAny history of epilepsy or a seizure disorder or any known prior seizures.Xx_NEWLINE_xXPatients will not be eligible if they present or have a history of seizure disorderXx_NEWLINE_xXFOR ALL PHASES (Ib AND II): Patients with seizure disorder requiring medicationXx_NEWLINE_xXAny chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a childXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlledXx_NEWLINE_xXPatients with history or presence of clinically significant neurological disorders such as epilepsy, generalized seizure disorder, severe brain injuries are ineligibleXx_NEWLINE_xXPre-existing (active or severe) neurologic disorders (e.g. pre-existing seizure disorder)Xx_NEWLINE_xXAdequate central nervous system function defined as:\r\n* Subjects with seizure disorder may be enrolled if on anticonvulsants and seizures are well controlledXx_NEWLINE_xXSeizure disorder requiring medicationXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXPatients with a history of active seizures (or a single confirmed seizure event) in the last 2 years from the time of registrationXx_NEWLINE_xXPrior history of psychiatric disorder or seizure disorders which could be exacerbated by Interleukin-2 as judged by the treating investigatorXx_NEWLINE_xXMedications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entryXx_NEWLINE_xXKnown brain metastases or history of seizureXx_NEWLINE_xXUncontrolled seizure disorder (ie, seizures within the past 2 months).Xx_NEWLINE_xXPatients with seizure disorder may be enrolled if receiving non-enzyme inducing anticonvulsants and well controlledXx_NEWLINE_xXMedications known to lower the seizure threshold (see list under prohibited meds) must be discontinued or substituted at least 4 weeks prior to study entryXx_NEWLINE_xXSeizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)Xx_NEWLINE_xXUncontrolled seizure disorder (ie, seizures within the past 2 months).Xx_NEWLINE_xXMedications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entryXx_NEWLINE_xXHistory of seizure or condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)Xx_NEWLINE_xXMedications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entryXx_NEWLINE_xXHistory of idiopathic seizure disorder, psychosis, or schizophreniaXx_NEWLINE_xXMedications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entryXx_NEWLINE_xXHistory of seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke or, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)Xx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months of day 1 visitXx_NEWLINE_xXKnown seizure disorderXx_NEWLINE_xXClinically evident CNS metastases or leptomeningeal disease not controlled by prior surgery or radiotherapy; history of seizure disorder not controlled by anti-seizure medication at the time of enrollment. Patients with primary CNS malignancies are excluded.Xx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXSeizure disorder requiring enzyme-inducing anti-epileptic drugs (EIAEDs)\r\n* Note: If the seizure disorder can be managed with agents that are not EIAEDs (e.g., levetiracetam or valproate), the patient should not be excludedXx_NEWLINE_xXREGORAFENIB EXCLUSION CRITERIA: Patients with seizure disorder requiring medicationXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXPatients with active seizure or history of seizure are not eligibleXx_NEWLINE_xXMedications known to lower the seizure threshold (see list under prohibited meds) must be discontinued prior to study entryXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months before day 1Xx_NEWLINE_xXPrior history of seizure disorderXx_NEWLINE_xXSeizure disorder requiring medicationXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure; history of loss of consciousness or transient ischemic attack within 12 months before day 1Xx_NEWLINE_xXHave a history of a seizureXx_NEWLINE_xXseizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma).Xx_NEWLINE_xXPatients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlledXx_NEWLINE_xXPatients with uncontrolled seizure disorder, spinal cord compression or carcinomatous meningitisXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlledXx_NEWLINE_xXDocumented uncontrolled seizure disorder– a seizure disorder controlled with medication (i.e. no seizures in the previous 6 months) will not exclude a patientXx_NEWLINE_xXAny chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a childXx_NEWLINE_xXPatients with prior history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold or other conditions predisposing to seizureXx_NEWLINE_xXPatients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsantsXx_NEWLINE_xXReports diagnosis of seizure disorderXx_NEWLINE_xXResearch participant does not have uncontrolled seizure activity following surgery prior to starting the first T cell doseXx_NEWLINE_xXResearch participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathyXx_NEWLINE_xXAny chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a childXx_NEWLINE_xXClinically evident central nervous system metastases or leptomeningeal disease not controlled by prior surgery or radiotherapy; history of seizure disorder not controlled by anti-seizure medication at the time of enrollment.Xx_NEWLINE_xXPatients with a seizure disorder are study eligible if seizures are controlled on anticonvulsantsXx_NEWLINE_xXPatients with any seizure disorderXx_NEWLINE_xXHistory or presence of clinically relevant CNS pathology such as uncontrolled seizure disorder, stroke, severe brain injuries, dementia, cerebellar disease or psychosisXx_NEWLINE_xXPatients with any history of seizure or seizure disorderXx_NEWLINE_xXHistory of seizure disorderXx_NEWLINE_xXPatients with known active brain metastases, a history of seizure disorder, or other neurological disorders/dysfunction, should be excluded from this clinical trialXx_NEWLINE_xXHistory of seizure disorderXx_NEWLINE_xXMedications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entryXx_NEWLINE_xXPatients with seizure disorder may be enrolled if well controlled; patients receiving enzyme-inducing anticonvulsants are not eligible for this study; patients must be off enzyme inducing anticonvulsant drugs (EIACD) for at least 2 weeks prior to registrationXx_NEWLINE_xXSubjects with seizure disorder may be enrolled if on anticonvulsants and well controlledXx_NEWLINE_xXHave a seizure disorder where > 1 seizure has occurred within the last year.Xx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure; history of loss of consciousness or transient ischemic attack within 12 months before day 1.Xx_NEWLINE_xXSeizure disorders requiring anticonvulsant therapy.Xx_NEWLINE_xXConcurrent use of anti-seizure drugs, with the exception of gabapentin for treatment of neuropathyXx_NEWLINE_xXPatients with seizure disorder requiring medication (such as steroid anti-epileptics)Xx_NEWLINE_xXPatients with seizure disorder may be enrolled if seizures are well-controlled (i.e., patients must not have required rescue medications for uncontrolled seizures within 14 days prior to enrollment)Xx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma)Xx_NEWLINE_xXHistory of seizure or condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system (CNS) or meningeal disease which may require treatment with surgery or radiation therapyXx_NEWLINE_xXMedications known to lower the seizure thresholdXx_NEWLINE_xXPast or current history of epilepsy or seizure disorder; exception: well-documented febrile seizure of childhoodXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXPatients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs will be excludedXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on anticonvulsants and well controlledXx_NEWLINE_xXNeurologic status\r\n* Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment\r\n* Patients with seizure disorders may be enrolled if seizures are well controlledXx_NEWLINE_xXHistory of seizure or any condition that may predispose subject to seizure (e.g., prior cortical stroke or significant brain trauma).Xx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure within 12 months prior to study treatment, including history of unexplained loss of consciousness or transient ischemic attackXx_NEWLINE_xXPrior treatment with medications known to lower the seizure threshold within 4 weeks of registrationXx_NEWLINE_xXSeizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)Xx_NEWLINE_xXActive seizure disorder uncontrolled by medicationXx_NEWLINE_xXPatient has no known history of seizure disorderXx_NEWLINE_xXUncontrolled seizure disorderXx_NEWLINE_xXPatients with a history of seizure disorder (except infant febrile seizures)Xx_NEWLINE_xXPatients with seizure disorder may be enrolled if well controlledXx_NEWLINE_xXActive seizure or history of seizure disorderXx_NEWLINE_xXKnown central nervous system (CNS) metastases or seizure disorder; patients with known brain metastases that have been successfully treated and stable for >= 6 months without requirement for corticosteroids and without seizure activity will be eligibleXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on anticonvulsants and if seizures are well controlledXx_NEWLINE_xXPatients with a high risk of seizures should be excluded from the protocol (e.g. those patients with an uncontrolled seizure disorder, and/or patients who have had a focal or generalized seizure within the last 12 months)Xx_NEWLINE_xXUncontrolled seizure disorderXx_NEWLINE_xXInadequate seizure controlXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXSeizure or cerebrovascular accident (CVA) in the last yearXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on anticonvulsants and well controlledXx_NEWLINE_xXUncontrolled, active seizure disorder or a history of seizureXx_NEWLINE_xXTreatment with non-enzyme inducing anti-seizure medications is allowedXx_NEWLINE_xXConcomitant medications that lower seizure thresholdXx_NEWLINE_xXCentral nervous system function defined as:\r\n* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled\r\n* Patients must not be in status, coma or assisted ventilation prior to study enrollmentXx_NEWLINE_xXPatients with a history of encephalitis, multiple sclerosis, or seizures within the last year (from seizure disorder or brain metastasis) should be excluded from this clinical trialXx_NEWLINE_xXPatients with active seizure or a history of seizure are not eligibleXx_NEWLINE_xXHistory of seizure disorder requiring antiepileptic medication or brain metastases with seizuresXx_NEWLINE_xXPatients must NOT have active seizure(s) or history of seizure(s)Xx_NEWLINE_xXPHASE II: Patients must NOT have active seizure(s) or history of seizure(s)Xx_NEWLINE_xXPatients with a history of seizure disorder requiring antiepileptics who have had a seizure episode within the last 6 monthsXx_NEWLINE_xXCentral nervous system function defined as\r\n* Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsantsXx_NEWLINE_xXPatients with history of seizure disorder requiring antiepileptics who have had a seizure episode within the last 6 monthsXx_NEWLINE_xXHistory of uncontrolled severe seizure disorderXx_NEWLINE_xXHistory of uncontrolled severe seizure disorderXx_NEWLINE_xXPatients who have an uncontrolled seizure disorder, or active neurological diseaseXx_NEWLINE_xXPatients must not have active, uncontrolled seizure disorder; patients must have had no seizures in the last 6 monthsXx_NEWLINE_xXFor Cohort C: Has a history of seizure or any condition that may predispose to seizureXx_NEWLINE_xXPatients who have had a seizure within 12 months prior to enrollment and patients receiving anti-convulsant therapy for a seizure disorder.Xx_NEWLINE_xXPatients must not have active seizure or history of seizureXx_NEWLINE_xXSubject has a history of seizure or any condition that may predispose to seizure.Xx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure;Xx_NEWLINE_xXPatients with seizure disorder requiring medication.Xx_NEWLINE_xXHistory of seizures or medications known to lower seizure thresholdXx_NEWLINE_xXUncontrolled seizure disorder, active neurological disease, or known CNS disease.Xx_NEWLINE_xXComorbid conditions: patients are unable to participate due to the following:\r\n* Generalized or partial seizure disorder that is uncontrolled at the time of registration; the definition of controlled generalized seizures is patients must be on a stable dose of anti-seizure medication and without generalized seizures for at least 10 days prior to registration; the definition of controlled partial seizures is patients must be on a stable dose of anti-seizure medication for at least 10 days prior to registration; patients with occasional breakthrough partial seizures are allowed at treating physician’s discretion\r\n* Grade 3 or 4 thromboembolic disease within 6 months (mo) of registration\r\n* Known history of prolonged QT syndromeXx_NEWLINE_xXThe subject has a history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma).Xx_NEWLINE_xXA history of seizure within 12 months prior to study entry.Xx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXPatients with seizure disorder requiring medication.Xx_NEWLINE_xXPatients with epilepsy, seizures, or predisposing factors for seizure as judged by the investigator.Xx_NEWLINE_xXUncontrolled seizure disorderXx_NEWLINE_xXPatients with a history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure thresholdXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and if seizures are well controlledXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXSubject has a history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma, encephalopathy within 3 months of Day 1).Xx_NEWLINE_xXHistory of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization); also, current or prior treatment with antiepileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months prior to randomizationXx_NEWLINE_xXseizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma).Xx_NEWLINE_xXHistory of seizure any time in the past for any reason or any condition that may predispose to seizures.Xx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXHas a history of seizureXx_NEWLINE_xXPatients with seizure disorder may be enrolled if seizures are well controlledXx_NEWLINE_xXHistory of seizure or any condition or concurrent medication that may predispose to seizureXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma, history of loss of consciousness or transient ischemic attack within 12 months of study entry); diabetics on a stable dose of insulin or antihyperglycemic regimen are allow if they have had no prior seizures and no history of loss of consciousness due to hypoglycemiaXx_NEWLINE_xXPatients with any seizure disorder requiring medicationXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXHistory of seizure or condition that may predispose to seizure (e.g., prior stroke within 1 year of starting study drug, brain arteriovenous malformation)Xx_NEWLINE_xXConcurrent therapy with medications known to have seizure potentialXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months of day 1 visitXx_NEWLINE_xXHistory of seizure or any condition or concurrent medication that may predispose to seizureXx_NEWLINE_xXPatients with known seizure disorder must have seizures adequately controlled with non-enzyme inducing antiepileptic medicationsXx_NEWLINE_xXpast history of seizure due to any cause except a single febrile seizure in childhood. Patients with a history of seizures should not have had a seizure within 12 months of Screening and must have had no anticonvulsants for 12 months prior to Screening,Xx_NEWLINE_xXcurrent use of medication that may lower seizure thresholdXx_NEWLINE_xXSubject has a history of seizure within the past 12 months of Screening as assessed by neurology examination and history.Xx_NEWLINE_xXMedications which lowers seizure thresholdXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism; also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (day 1 visit)Xx_NEWLINE_xXHistory of epilepsy or seizure disorderXx_NEWLINE_xXNo history of seizure or any condition that may increase the patient’s seizure risk (e.g., prior cortical stroke, significant brain trauma); no history of transient ischemic attack (TIA) within 12 months of enrollmentXx_NEWLINE_xXHistory of seizure or condition that may pre-dispose to seizureXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma, history of loss of consciousness or transient ischemic attack within 12 months of study entry) or concurrent medication that may predispose to seizure; diabetics on a stable dose of insulin or antihyperglycemic regimen are allowed if they have had no prior seizures and no history of loss of consciousness due to hypoglycemiaXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma); also, history of loss of consciousness or transient ischemic attack within 12 months of enrollmentXx_NEWLINE_xXHistory of idiopathic seizure disorder, psychosis or schizophreniaXx_NEWLINE_xXAny history of seizure or condition that may predispose to seizureXx_NEWLINE_xXHistory of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack, or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization)Xx_NEWLINE_xXPatients with history of seizure as an adult including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization); also, current or prior treatment with anti-epileptic medications for the treatment of seizures or history of loss of consciousness; also transient ischemic attack within 12 months prior to randomization will not be permittedXx_NEWLINE_xXAny history of seizure or a condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy).Xx_NEWLINE_xXConcurrent therapy with medications known to have seizure potential (those must have been discontinued or substituted for at least 28 days prior to starting the trial)Xx_NEWLINE_xXNo history of seizures or medical conditions which may lower seizure thresholdXx_NEWLINE_xXAny history of seizures or medical condition which lowers seizure thresholdXx_NEWLINE_xXPatients with seizure disorder may be enrolled if on anticonvulsants and well controlledXx_NEWLINE_xXPatients with uncontrolled seizure disordersXx_NEWLINE_xXNo uncontrolled seizure disordersXx_NEWLINE_xXA history of uncontrolled seizure disorderXx_NEWLINE_xXPatients must not have a history of any type of seizure for at least 10 years prior to registration.Xx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXSeizure disorderXx_NEWLINE_xXConcurrent treatment with medications known to have seizure potentialXx_NEWLINE_xXHistory of seizure or condition that may predispose to seizureXx_NEWLINE_xXPatients must not have uncontrolled central nervous system disease; patients with a history of seizure disorders must be seizure-free for one year prior to enrollmentXx_NEWLINE_xXPatients with seizure disorder may be enrolled if well controlledXx_NEWLINE_xXActive central nervous system (CNS) disorder or seizure disorderXx_NEWLINE_xXUncontrolled seizure disorder or other serious neurological diseasesXx_NEWLINE_xXSubjects with seizure disorder currently requiring medication.Xx_NEWLINE_xXPast or current history of epilepsy or seizure disorderXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure.Xx_NEWLINE_xXHave a seizure disorder requiring medication.Xx_NEWLINE_xXSeizure disorders requiring anticonvulsant therapyXx_NEWLINE_xXHistory of seizure disorderXx_NEWLINE_xXPatients with predisposing factors for seizure including history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastasis, and brain arteriovenous malformationXx_NEWLINE_xXPrior history of seizure disorderXx_NEWLINE_xXHistory of (a) seizure or any condition that may predispose to seizure (prior cortical stroke or significant brain trauma); (b) loss of consciousness or transient ischemic attack within 12 months prior to day 1 of cycle 1.Xx_NEWLINE_xXUncontrolled seizure disorder or active neurologic diseaseXx_NEWLINE_xXKnown brain metastases, uncontrolled seizure disorder, or active neurologic diseaseXx_NEWLINE_xXKnown brain metastases, uncontrolled seizure disorder, or active neurologic diseaseXx_NEWLINE_xXHistory of seizure disordersXx_NEWLINE_xXAny history of brain metastases or prior seizure or conditions predisposing to seizure activityXx_NEWLINE_xXSubjects with seizure disorder may be enrolled if on anticonvulsants and seizures are well controlledXx_NEWLINE_xXHistory of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold (not applicable to patients who have already been treated with enzalutamide in first line before inclusion).Xx_NEWLINE_xXCNS primary malignancies, active seizure disorder or spinal cord compression, or carcinomatous meningitis.Xx_NEWLINE_xXHistory of seizures (unless seizure free for 5 years);Xx_NEWLINE_xXUncontrolled seizure disorder or active neurologic diseaseXx_NEWLINE_xXUncontrolled seizure disorder or active neurologic diseaseXx_NEWLINE_xXUncontrolled seizure disorder requiring therapy (such as steroids or anti-epileptics with significant CYP interaction)Xx_NEWLINE_xXFocal or generalized seizure within the last 12 months.Xx_NEWLINE_xXSeizure disorder requiring anticonvulsant therapy (such as steroids or anti-epileptics)Xx_NEWLINE_xXUncontrolled seizure activity.Xx_NEWLINE_xXUncontrolled seizure disorder.Xx_NEWLINE_xXHistory of seizure disorder not related to underlying cancer.Xx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (Day 1 visit)Xx_NEWLINE_xXHistory of seizure or any condition that may predispose subject to seizure (e.g., prior cortical stroke or significant brain trauma). History of loss of consciousness or transient ischemic attack within 12 months of randomizationXx_NEWLINE_xXEvidence of significant central nervous system disease including seizure disorder requiring medication, symptomatic metastatic brain or meningeal tumorsXx_NEWLINE_xXUse of a medication known to lower the seizure threshold within 28 days of first dose of study drugXx_NEWLINE_xXHistory of seizureXx_NEWLINE_xXPatients with active seizures or a history of seizure are not eligible for study entry, with the exception of patients with documented febrile seizureXx_NEWLINE_xXDonor must have adequate neurologic function as defined by NO evidence of a severe central or peripheral neurologic abnormality and no history of cerebrovascular accident or seizure disorder requiring anticonvulsant medication.Xx_NEWLINE_xXUncontrolled seizure disorder. Use of cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital) is not allowed throughout the entire study.Xx_NEWLINE_xXCentral Nervous System: Patients without seizure disorder OR patients with well-controlled seizure disorder receiving anticonvulsants may be enrolled on this protocol; anticonvulsants must not be enzyme-inducing (inducers of CYP3A, i.e., no barbiturates, phenytoin, carbamazepine, etc.)Xx_NEWLINE_xXPrior seizures < 3 months prior to enrollment. Subjects with a history of seizure disorders ? 3 months prior to enrollment must be seizure free and on stable anticonvulsant medication(s) for ? 3 months prior to enrollment).Xx_NEWLINE_xXUncontrolled seizure disorder, active neurological disease, or greater than Grade 2 neuropathy.Xx_NEWLINE_xXPatients with seizure disorder may be enrolled if on anticonvulsants and well-controlled; central nervous system (CNS) toxicity < grade 2Xx_NEWLINE_xXSubjects with uncontrolled seizureXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXSeizure disordersXx_NEWLINE_xXHave a known history of central nervous system disease (e.g., brain metastases or a seizure disorder)Xx_NEWLINE_xXHistory of intractable epilepsy, or uncontrolled seizure disorderXx_NEWLINE_xXPatients with bradycardia, seizure disorder or peptic ulcer disease (PUD)Xx_NEWLINE_xXIntractable seizures while on adequate anticonvulsant therapy—more than 1 seizure per week for the past 2 monthsXx_NEWLINE_xXPatients must have adequate seizure control and be on a stable, or decreasing, dose of anti-epilepticsXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months of day 1 visitXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months of the day 1 visitXx_NEWLINE_xXFor patients with CNS tumors (primary or metastatic), any baseline neurologic deficits (including seizure) must be stable for at least one week prior to study enrollmentXx_NEWLINE_xXMedications known to lower the seizure threshold must be discontinued or substituted prior to study treatmentXx_NEWLINE_xXHistory of seizure or any condition or concurrent medication that may predispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within one year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)Xx_NEWLINE_xXHistory of a seizure disorder diagnosis or have experienced a seizure in the past 12 monthsXx_NEWLINE_xXHistory of significant neurological disease including poorly controlled seizures (i.e., > 1 seizure per month; anti-epileptic medications are acceptable), stroke, or head injury with loss of consciousnessXx_NEWLINE_xXPATIENTS: History of neuroleptic malignant syndrome or active seizure disorder (with seizure episode within the past week)Xx_NEWLINE_xXPatient has an active seizure disorder; (patients with a previous history of seizure disorders will be eligible for the study, if they have had no evidence of seizure activity, and they have been free of anti-seizure medication for the previous 5 years)Xx_NEWLINE_xXSurvivors who report ever being diagnosed with a seizure disorder or have experienced a seizure in the past 12 months will be excludedXx_NEWLINE_xXPatients on any anti-seizure medications, such as gabapentin or Lyrica, specifically for chronic management less than 24 hours prior to surgeryXx_NEWLINE_xXPatients who have a history of head injury or who have known seizure activityXx_NEWLINE_xXHistory of seizure disorderXx_NEWLINE_xXPatients with seizure disorders treated with anticonvulsantsXx_NEWLINE_xXHistory of seizure or currently taking anti-epileptic medicationXx_NEWLINE_xXPatients who have a history of head injury or who have known seizure activity.Xx_NEWLINE_xXHave a history of seizure or loss of consciousnessXx_NEWLINE_xXIntractable seizures while on adequate anticonvulsant therapy—more than 1 seizure per month for the past 2 monthsXx_NEWLINE_xXUncontrolled seizure disorderXx_NEWLINE_xXPatients with seizure disorder requiring medicationXx_NEWLINE_xXAny history of brain metastases or prior seizure or conditions predisposing to seizure activityXx_NEWLINE_xXHistory of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization); also, current or prior treatment with antiepileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months of enrollmentXx_NEWLINE_xXHistory of a seizure disorder or requirement for anti-seizure medicationXx_NEWLINE_xXWearing a pacemaker or implantable cardioverter-defibrillator; uncontrolled seizure disorderXx_NEWLINE_xXUncontrolled seizure disorderXx_NEWLINE_xXParticipant has uncontrolled seizure disorder in past 12 monthsXx_NEWLINE_xXPatient must not have a seizure disorderXx_NEWLINE_xXSubjects with a history of seizure disorder taking anti-seizure medication within 30 days prior to randomization.Xx_NEWLINE_xXSeizure disorderXx_NEWLINE_xXDocumentation of history of seizure within previous 5 yearsXx_NEWLINE_xXKnown history of epilepsy/seizure disorderXx_NEWLINE_xXPatients with prior seizure history who have experienced a seizure within the three months prior to enrollment are excludedXx_NEWLINE_xXHistory of epileptic disorder or any seizure history unrelated to tumorXx_NEWLINE_xXPatients receiving glucocorticoids and/or anti-seizure medications are eligible for this studyXx_NEWLINE_xXHistory of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack, or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization)Xx_NEWLINE_xXUnstable medical condition, such as ischemic heart disease, or any other disease or medical condition that may place the patient at added risk during the study, as assessed by the Principal Investigator. A patient with a seizure disorder, focal or generalized, not adequately controlled by anti-convulsant therapy, and /or patient who have experienced an event of focal or generalized seizure within 7 days prior to screening will be considered neurologically unstable.Xx_NEWLINE_xXHuntington’s disease, hydrocephalus or seizure disorderXx_NEWLINE_xXPatients with a seizure disorder are eligible if well-controlled on anticonvulsants; if on a non-enzyme inducing anticonvulsant, the irinotecan (irinotecan hydrochloride) dose will be adjusted as outline in treatment planXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the pastXx_NEWLINE_xXHistory of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack, or any condition that may predispose to seizure (e.g. prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization)Xx_NEWLINE_xXHistory of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvementXx_NEWLINE_xXSeizure disorderXx_NEWLINE_xXPatients with a seizure history will not be permitted on protocol; patients on anticonvulsant medications will not be permitted on studyXx_NEWLINE_xX