Histologically proven diagnosis of glioblastoma (World Health Organization [WHO] grade IV) confirmed by central review prior to step 2 registration Participants must have histologically confirmed newly diagnosed glioblastoma or glioblastoma variant (example [ex.] gliosarcoma), including documentation of unmutated isocitrate dehydrogenase (IDH) by immunohistochemistry or sequencing Patients must have a newly-diagnosed glioblastoma or gliosarcoma that has been confirmed pathologically by a board-certified neuropathologist Patients must have histologically or cytologically confirmed glioblastoma or other grade IV malignant glioma (i.e. gliosarcoma, small cell glioblastoma, etc.), recurrent after prior external beam fractionated radiotherapy and temozolomide chemotherapy Participants must have histologically confirmed glioblastoma or variants; subjects with initial diagnosis of a lower grade glioma are eligible if a subsequent biopsy is determined to be glioblastoma or variants Patients must have histologically confirmed diagnosis of glioblastoma multiforme (GBM) or anaplastic glioma, World Health Organization (WHO) grade 3 or 4 Has known glioblastoma multiforme of the brainstem recurrent glioblastoma Glioblastoma. Patients must have a newly-diagnosed glioblastoma or gliosarcoma that has been confirmed pathologically Participants must have histologically confirmed glioblastoma and evidence of recurrence > 2 months since last cycle of temozolomide or other alkylating agent; patients with low-grade tumors who have progressed to glioblastoma are eligible Patients with histologically confirmed glioblastoma or other grade IV malignant glioma (i.e. gliosarcoma, small cell glioblastoma, etc.), recurrent after prior external-beam fractionated radiotherapy and temozolomide chemotherapy Patients must have histologically proven glioblastoma or gliosarcoma which is progressive or recurrent (per RANO criteria) following radiation therapy and temozolomide Histopathological evidence of glioblastoma or gliosarcoma, World Health Organization (WHO) grade IV Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme), established by biopsy or resection not more than 3 months prior to registration Histopathologically proven diagnosis of glioblastoma or gliosarcoma prior to registration by pathology report Histological confirmation of supratentorial glioblastoma (also known as astrocytoma grade IV, gliosarcoma) amenable to surgical resection =< 28 days prior to registration Patients must have histologically proven glioblastoma multiforme (GBM) or gliosarcoma (GS) Have histologically confirmed World Health Organization grade IV malignant glioma (glioblastoma or gliosarcoma); participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made Newly diagnosed, histologically-confirmed supratentorial World Health Organization (WHO) grade IV gliomas including glioblastoma (all variants) and gliosarcoma Previous histologic diagnosis of glioblastoma, transformation to glioblastoma or gliosarcoma established by biopsy or resection prior to enrollment as evident on National Institutes of Health (NIH) or outside pathology Histopathologically proven newly-diagnosed, supratentorial glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Have histologically confirmed World Health Organization grade IV malignant glioma (glioblastoma or gliosarcoma); participants will also be eligible if the original histology was lower grade glioma and there is suspected transformation to glioblastoma based on imaging findings; if the final pathology report after resection fails to confirm recurrent glioblastoma or gliosarcoma, the subject will be followed for adverse events (AEs) and survival, but excluded for other primary and secondary objective analysis; the subject will be replaced PHASE II DOSE EXPANSION IN NEWLY DIAGNOSED GBM: Have histologically confirmed World Health Organization grade IV glioma (glioblastoma or gliosarcoma) PHASE I: Have histologically confirmed World Health Organization WHO grade IV glioma (glioblastoma or gliosarcoma); participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made Histologically confirmed diagnosis of World Health Organization grade IV malignant glioma (glioblastoma or gliosarcoma) Histopathologically confirmed glioblastoma or gliosarcoma (WHO Grade IV) confirmed by local pathology tissue screening. Radiologic evidence of first recurrence after initial treatment (including surgery, radiation, and temozolomide) or tumor refractory to initial treatment without subsequent treatment in glioblastoma or gliosarcoma (WHO Grade IV). Transformation from a lower grade glioma previously treated with radiation and/or temozolomide to glioblastoma will be considered first recurrence for the purpose of this trial Histologically confirmed glioblastoma multiforme, World Health Organization (WHO) grade IV astrocytoma Patients must have histologically or cytologically confirmed glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma Patients with recurrent or progressive glioblastoma or other grade IV malignant glioma (e.g. glioblastoma, gliosarcoma, giant cell glioblastoma, etc.) who have failed prior radiation but who have not progressed/recurred on bevacizumab; patients will be eligible if the original histology was lower-grade glioma and subsequent diagnosis of glioblastoma or gliosarcoma is made Histologic diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) First or second relapse of glioblastoma Histologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) Participants must have histologically confirmed intracranial glioblastoma or gliosarcoma following maximum surgical resection; tumors primarily localized in the infratentorial compartment will be excluded Participants may have had prior surgery for glioblastoma or gliosarcoma but no systemic or radiation therapy Participants will not be eligible if the original diagnosis was a lower grade glioma and a subsequent histologic diagnosis revealed glioblastoma Histologically confirmed glioblastoma or gliosarcoma in 1st, 2nd or 3rd relapse. Glioblastoma or gliosarcoma disease with leptomeningeal spread. Newly diagnosed, histologically-confirmed supratentorial World Health Organization (WHO) grade IV gliomas including glioblastoma (all variants) and gliosarcoma. Have histologically confirmed World Health Organization grade IV glioma (glioblastoma [GB] or gliosarcoma). Newly diagnosed histologically confirmed unmethylated glioblastoma multiforme (World Health Organization [WHO] grade IV). Patients with secondary glioblastoma, in particular those who are IDH1 or IDH2 mutant, will not be excluded. Unmethylated MGMT must be confirmed by a polymerase chain reaction (PCR)-based assay. Histologically-confirmed intracranial glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) with evidence of clinical and radiographic (computed tomography [CT] or MRI brain) tumor progression (need not be biopsy proven) Part 1 patients must have prior histologically proven glioblastoma that is progressive or recurrent following radiation therapy +/- chemotherapy Part 2 patients must have histologically confirmed glioblastoma or gliosarcoma A single glioblastoma or gliosarcoma tumor with histopathological confirmation for first or presenting second recurrence of glioblastoma or gliosarcoma at the time of consent Pathologically confirmed World Health Organization (WHO) grade IV glioblastoma or variants (gliosarcoma, glioblastoma with oligodendroglial features, giant cell glioblastoma) with adequate tumor material for genomic sequencing; participants will be eligible if the original diagnosis was a lower grade glioma and a subsequent histologic diagnosis of glioblastoma or its variants was made, and they received no prior therapy other than surgery Patients must have histologically confirmed glioblastoma that is progressive or recurrent following radiation therapy and temozolomide Histopathologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) following either a surgical resection or biopsy 1d. Glioblastoma -Enrollment Completed Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma). Histologically confirmed glioblastoma. A local pathology report constitutes adequate documentation of histology for study inclusion. Patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy was determined to be glioblastoma. First or second progression of Glioblastoma; Confirmation by central pathology review of WHO grade IV glioblastoma or gliosarcoma Newly diagnosed histologically confirmed glioblastoma multiforme (World Health Organization [WHO] grade IV); patients with secondary glioblastoma, in particular those who are IDH1 or IDH2 mutant, will not be excluded Histopathologically proven diagnosis of glioblastoma or gliosarcoma prior to registration by pathology report Histologically confirmed newly diagnosed glioblastoma; patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy was determined to be glioblastoma and they received no prior treatment Pathologically confirmed diagnosis of glioblastoma multiforme (GBM); or World Health Organization (WHO) grade IV (gliosarcoma) Histologically confirmed glioblastoma Have histologically confirmed World Health Organization grade IV malignant glioma (glioblastoma or gliosarcoma); participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made Have histologically confirmed World Health Organization grade IV malignant glioma (glioblastoma or gliosarcoma); participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made Glioblastoma or gliosarcoma in first or second recurrence only Any recurrence of a glioblastoma multiforme Patients must have tissue confirmation of high grade (World Health Organization [WHO] grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma with oligodendroglial features, glioblastoma with primitive neuroectodermal tumor (PNET) features Histological diagnosis of: glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) adapted recursive partitioning analysis (RPA) class III, IV, or V Prior radiation or chemotherapy for glioblastoma or glioma. Patients must have histologically confirmed diagnosis of glioblastoma multiforme (GBM) or anaplastic glioma, World Health Organization (WHO) grade 3 or 4 Patients with histologically proven supratentorial glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV astrocytoma) will be eligible for this protocol; patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or gliosarcoma is made prior to any definitive treatment (radiotherapy, chemotherapy) GBM patients only (enrollment plan 1)\r\n* Histologically confirmed glioblastoma multiforme World Health Organization (WHO) grade III-IV with recurrent or progressive disease after standard therapy\r\n* Age 16 years and older Part C: Glioblastoma multiforme that has progressed or recurred after radiotherapy and/or chemotherapy Patients will have histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS); this includes treatment-naive patients with prior tissue diagnosis of lower grade gliomas that have been upgraded after repeat resection Patients with glioblastoma multiforme or gliosarcoma Patients with histologically proven supratentorial WHO grade IV glioma (glioblastoma or gliosarcoma) will be eligible for the study. Prior treatment for glioblastoma or gliosarcoma. Prior treatment with a PI3K and/or mTOR inhibitors for glioblastoma or for pre-existing neoplasm transformed to glioblastoma (applicable for combination treatment arm only) Histologically confirmed glioblastoma multiforme or gliosarcoma Glioblastoma or gliosarcoma disease with leptomeningeal spread Participants with glioblastoma are eligible for this study; these will include\r\n* Those with a histologically proven diagnosis of glioblastoma who have developed new changes on MRI following primary treatment\r\n* Those who received primary treatment for a histologically proven lower grade (2 or 3) glioma and who now progress with radiographic characteristics of transformed glioma Histologically confirmed GBM or World Health Organization (WHO) Grade IV variants (gliosarcoma, glioblastoma with oligodendroglial features, or giant cell glioblastoma). Patients will be eligible if the original histology was lower grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made. Must have histologically proven glioblastoma Patients must have prior histologically proven glioblastoma that is progressive or recurrent following radiation therapy +/- chemotherapy Patient with histologically demonstrated, previously untreated glioblastoma Patients must have histologically confirmed diagnosis of a recurrent/progressive World Health Organization (WHO) grade IV malignant gliomas (glioblastoma multiforme and gliosarcoma) Histologically proven diagnosis of glioblastoma or other grade IV malignant glioma (including variants of glioblastoma i.e., gliosarcoma, giant cell glioblastoma, etc.). Diagnoses excluded include: glioblastoma multiforme, gliosarcoma, diffuse pontine glioma, or other tumors presumed to have expected median survival per the investigators of less than 1 year Patients must have histologically proven glioblastoma or gliosarcoma which is progressive or recurrent following radiation therapy +/- chemotherapy Histologically confirmed supratentorial glioblastoma or other WHO grade III or IV malignant glioma from archival tissue. Histologically proven intracranial glioblastoma or gliosarcoma at initial surgery\r\n* Patients will be eligible if the original histology was low-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made (high-grade transformation) Participants must have histologically confirmed glioblastoma and evidence of recurrence; patients with low-grade tumors who have progressed to glioblastoma are eligible Participants must have histologically confirmed glioblastoma and evidence of possible tumor progression on imaging; patients with low-grade tumors who have progressed to glioblastoma are eligible Primary diagnosis of a glioblastoma Participants must have histologically or cytologically confirmed newly-diagnosed glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV/IV) and be planning to undergo standard chemoradiation treatment Participants with multifocal or recurrent glioblastoma Confirmation of pathology as glioblastoma newly diagnosed glioblastoma or recurrent/suspected recurrent glioblastoma Patients with glioblastoma multiforme