Few studies have addressed radiomics based differentiation of Glioblastoma (GBM) and intracranial metastatic disease (IMD). However, the effect of different tumor masks, comparison of single versus multiparametric MRI (mp-MRI) or select combination of sequences remains undefined. We cross-compared multiple radiomics based machine learning (ML) models using mp-MRI to determine optimized configurations. Our retrospective study included 60 GBM and 60 IMD patients. Forty-five combinations of ML models and feature reduction strategies were assessed for features extracted from whole tumor and edema masks using mp-MRI [T1W, T2W, T1-contrast enhanced (T1-CE), ADC, FLAIR], individual MRI sequences and combined T1-CE and FLAIR sequences. Model performance was assessed using receiver operating characteristic curve. For mp-MRI, the best model was LASSO model fit using full feature set (AUC 0.953). FLAIR was the best individual sequence (LASSO-full feature set, AUC 0.951). For combined T1-CE/FLAIR sequence, adaBoost-full feature set was the best performer (AUC 0.951). No significant difference was seen between top models across all scenarios, including models using FLAIR only, mp-MRI and combined T1-CE/FLAIR sequence. Top features were extracted from both the whole tumor and edema masks. Shape sphericity is an important discriminating feature.